Elafibranor upregulates the EMT-inducer S100A4 via PPARβ/δ.

Details

Serval ID
serval:BIB_A17232EDFD55
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Elafibranor upregulates the EMT-inducer S100A4 via PPARβ/δ.
Journal
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
Author(s)
Zhang M., Barroso E., Ruart M., Peña L., Peyman M., Aguilar-Recarte D., Montori-Grau M., Rada P., Cugat C., Montironi C., Zarei M., Jurado-Aguilar J., Camins A., Balsinde J., Valverde Á.M., Wahli W., Palomer X., Vázquez-Carrera M.
ISSN
1950-6007 (Electronic)
ISSN-L
0753-3322
Publication state
Published
Issued date
11/2023
Peer-reviewed
Oui
Volume
167
Pages
115623
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Elafibranor is a dual peroxisome proliferator-activated receptor (PPAR)α and β/δ agonist that has reached a phase III clinical trial for the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we examined the effects of elafibranor in mice fed a choline-deficient high-fat diet (CD-HFD), a model of metabolic dysfunction-associated steatohepatitis (MASH) that presents obesity and insulin resistance. Our findings revealed that elafibranor treatment ameliorated steatosis, inflammation, and fibrogenesis in the livers of CD-HFD-fed mice. Unexpectedly, elafibranor also increased the levels of the epithelial-mesenchymal transition (EMT)-promoting protein S100A4 via PPARβ/δ activation. The increase in S100A4 protein levels caused by elafibranor was accompanied by changes in the levels of markers associated with the EMT program. The S100A4 induction caused by elafibranor was confirmed in the BRL-3A rat liver cells and a mouse primary hepatocyte culture. Furthermore, elafibranor reduced the levels of ASB2, a protein that promotes S100A4 degradation, while ASB2 overexpression prevented the stimulating effect of elafibranor on S100A4. Collectively, these findings reveal an unexpected hepatic effect of elafibranor on increasing S100A4 and promoting the EMT program.
Keywords
Animals, Mice, Rats, Diet, High-Fat, Epithelial-Mesenchymal Transition, Liver, Non-alcoholic Fatty Liver Disease/metabolism, PPAR delta/metabolism, PPAR-beta/agonists, PPAR-beta/metabolism, PPAR-beta/therapeutic use, ASB2, EMT, Elafibranor, MASLD, PPARβ/δ, S100A4
Pubmed
Web of science
Open Access
Yes
Create date
06/10/2023 13:41
Last modification date
25/11/2023 7:08
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